Please pardon my ignorance but trying to understand the significance of JAK2.
First question is when some posters here say they are JAK2 -ve, does that mean they don’t have the JAK2 mutation? Not some actual -ve variant!
Second question is that I assume Jakafi would only be used on JAK2 patients? However, if it merely suppresses the JAK2 mutation, what controls the underlying PV/ET?
Trying to understand the impact of JAK2 on ET/PV and treatment plans.
Hi Paul, I’m Jak2 negative and from what I was told by my haem, I understand that I don’t have the mutation of the Jak2 gene but other mutations will have occurred which have caused my PV. Perhaps Maz can confirm this is correct, just to make sure I’m not giving you wrong info.
Kind regards Aime xx😺
Also, how relevant is the % JAK2 allele burden? This seems a risk factor insomuch as the lower the better? I was given mine with my initial diagnosis - 56.8% mutant allele burden.
Think it’s naturally higher for PV patients than ET?
hi Paul, this information on our website might help
mpnvoice.org.uk/about-mpns/...
and this also might help
ncbi.nlm.nih.gov/pmc/articl...
best wishes, Maz
Hi Paul, below is a link to a brief article on allele burden. Hope it helpful.
Mary
From what I understand JAK2 is a groundbreaking discovery within the last few years and they believe it is somehow related to PMF, ET and PV as most patients (i.e. >50%) have the JAK2 mutation. I may be wrong but some people may have the JAK2 gene their entire life without even knowing and never transform to PMF/ET or PV.
The discovery of JAK gene alone will see some huge advances in medication going forward (e.g. Ruxolitnib - released for use in the last 2 years - mainly for PMF patients currently).
Whether it is positive or negative JAK2 I'm not sure is of any major significance - I would ask your hematologist. From what I understand PV/ET are degenerative conditions which increase the risk of transforming to Myelofibrosis or Leukemia with age, however it varies from person to person. Jakabi, Hydrea, Interferon and more recently Ruxolitinib, appear to be drugs that slow things down and reduce the symptoms/side effects. In 10 years time there will probably be twice as many more powerful options available.
I'm relatively new to these diseases but am meeting with the hematologist in a couple of weeks so will learn more then.
Thanks. I’m particularly interested in the significance of high Allele Burden as a risk factor for progression to MF. One study I read concluded that an AB over 50% significantly increase risk of progression to MF. This applied to PV patients, ET have a much lower AB.
I know that Maz says that /// don’t focus AB results (which is reassuring) but if this is a good indicator of increased MF risk, should not high AB PV patients have more regular BMBs?
And perhaps more importantly, be treated with say Jakafi at an earlier stage to reduce AB if it is the AB alone that is the risk factor?
One study reported a rather alarming 40% risk increase for every 10% AB increase over 50%. However we all know how misleading statistics can be.
I’m have a BMB tomorrow so will ask my hemo all about this and report back. I suspect answer will be yes, increased risk but not that much. I’m more interested in whether Jakafi (and possibly Ropeginterferon?) reduces this risk.
Saw my hemo for BMB yesterday. One word of advice for anyone on aspirin is to discuss this with your specialist pre BMB. I took a 75mg on Monday morning and then stopped ahead of BMB Thurs. Took well over an hour to stop the bleeding. No big deal since not much blood but best avoided if you can, if only to save on your washing bill!
Re AB, my guy confirmed that it is a risk factor re progression to MF but there are other issues so not a clear early warning indicator. He seemed quite relaxed about my 60% AB.
My take is that it’s worth knowing your AB (it’s a blood test, not part of BMB) and if it’s higher than normal, just be aware that you are a bit more at risk. Hence if offered a BMB it might then sway your decision to say yes just to clarify exactly what’s going on.
I Am led to believe that the jak 2 is the mutant in the bone marrow that keeps multiplying the blood. If you have jak 2 - it is not as serious. But don’t quote me on this. I thought they used jakafi for spleen swelling. Which is a sign of progression of the disease. Pv and Et on there own without jak2. Is still serious but not as bad if you have jak2. But I may be misimformed about my theory
I had the same conversation with my consultant two weeks ago as I do not understand it either! I have ET and I actually wrote down what my consultant told me when I asked him to explain what my results means:
CALR-Mutation- JAK2 neg.
MPL-Triple neg.
My understanding of this is I do not have the mutation gene
I am JAK +ve and my understanding is a mutation in the JAK2 gene causes the problem. I have not had a BMB so do not know what my allele burden is. I am on hydroxy and asprin and I my understanding is that the treatment would not be affected by the reading, whilst my blood levels are being controlled -which they have been, thankfully for over a year.
Hi Paul,
I don't wish to confuse the issue even further, but in some rare cases Jakavi is used for Jak2-ve patients !
I had an SCT due to my MF+MDS-u condition I was 'triple -ve' ie. I had none of the common mutations and consequently was Jak2-ve. Following a severe liver GVHD that was unresponsive to the classic treatment by cortisone I was treated using Jakavi.
In this scenario the Jakavi is used for its immunosuppressive properties. Fortunately for me this seems to have worked and I'm hoping to be able to stop this treatment in the very near future.
Happy Christmas to all.
Gary
This is from 2013 but still very interesting re the debate on HU v Peg and whether Peg reduces progression and even fibrosis. The $1m question is whether it merely treats the ‘symptoms’, giving a false impression of slowing the underlying progression.
If this was known in 2013, you would have thought the picture in 2017 would be clearer.
Immunotherapy, early research for Jak2
Polycythemia Jak2 negative
Outcomes of JAK2 V617F-positive polycythemia vera and ET according to the JAK2 V617F allele burden
Ladies, contraception and ET JAK2
